Serum SIRT1 Levels and Gene Polymorphisms in Breast Cancer: A Biomarker and Genetic Association Study

Silent mating type information regulation 2 homolog (SIRT1), a key protein involved in cellular regulation, exhibits altered expression in breast cancer. The study aimed to assess serum Sirtuin 1 level, investigate SIRT1 gene polymorphisms, and examine their association with breast cancer. One hundred seventy-two breast cancer patients and 78 healthy age-matched females were included in the study. Genetic variants of the SIRT1 gene were identified using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism/Sanger Sequencing and serum SIRT1 levels using Enzyme-Linked Immuno Sorbent Assay. Serum SIRT1 levels were significantly higher in breast cancer patients [0.822 (0.72-0.96)] than controls [0.752 (0.66-0.86)], p = 0.0027. Subgroup analyses revealed notable increases in Human epidermal growth factor receptor 2-positive (p = 0.0016), hormone-positive (p = 0.0232), and Triple Negative Breast Cancer groups (p = 0.4426) compared to the control group. The SIRT1 levels were also significantly associated with breast cancer (p = 0.0252). SIRT1 exhibited an Area Under Curve (AUC) of 0.618, with 58% sensitivity and specificity at a cutoff of 0.797, showing poor discriminative ability. rs141528984 had a significant difference in allele frequency between patient group and control group (OR = 3.48, 95% CI: 1.896-6.516), p < 0.0001. There were no significant associations between SIRT1 gene polymorphisms and serum Sirtuin 1 levels in breast cancer patients. The proliferation marker Ki67 showed a significant association (p = 0.0428) with specific SIRT1 variants, rs777323664, rs757804740, and rs184282868. SIRT1 levels are elevated in breast cancer patients indicate its potential as a diagnostic marker. Mutant alleles of rs141528984 were more common in controls compared to case group, indicating its protective function. Ki67 expression was associated with rs777323, rs757804740, and rs1842828683 which may contribute to tumor aggressiveness.